CN109721566B - Preparation method of 1- (4-morpholine phenyl) -1-butanone - Google Patents
Preparation method of 1- (4-morpholine phenyl) -1-butanone Download PDFInfo
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- CN109721566B CN109721566B CN201711026617.0A CN201711026617A CN109721566B CN 109721566 B CN109721566 B CN 109721566B CN 201711026617 A CN201711026617 A CN 201711026617A CN 109721566 B CN109721566 B CN 109721566B
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Abstract
The invention relates to a preparation method of an alpha-aminobenzophenone photoinitiator intermediate, and in particular relates to a preparation method of 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) butanone and a 2- (4-methylbenzyl) -2-dimethylamino-1- (4-morpholinophenyl) butanone intermediate 1- (4-morpholinophenyl) -1-butanone as a photoinitiator. Overcomes the defects in the prior art, and provides a preparation method of the alpha-aminophenylacetic acid ketone photoinitiator intermediate, which does not need to add heavy metal catalyst, does not need to add materials at high temperature and high pressure, has simple post-treatment and good product appearance and is suitable for industrial production.
Description
Technical Field
The invention relates to a preparation method of an alpha-aminobenzophenone photoinitiator intermediate, and in particular relates to a preparation method of 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) butanone and a 2- (4-methylbenzyl) -2-dimethylamino-1- (4-morpholinophenyl) butanone intermediate 1- (4-morpholinophenyl) -1-butanone as a photoinitiator.
Background
The alpha-aminoketone photoinitiator is an important photoinitiator, wherein 2-benzyl-2-dimethylamino-1- (4-morpholinyl phenyl) butanone and 2- (4-methylbenzyl) -2-dimethylamino-1- (4-morpholinyl phenyl) butanone are alpha-aminoketone photoinitiators developed by Ciba company, trade names are Irgacure 369 and Irgacure 379 respectively, the photoinitiators have good thermal stability, long storage period, good solubility, light color, good yellowing resistance, high photocuring speed and good deep curing performance, are particularly used for colored systems, are widely applied in the field of UV curing, and are widely applied to the fields of photocuring coatings, printing inks, photoresists and the like.
The preparation method mainly comprises two methods, one is that fluorobenzene is taken as a raw material (US 5534629A), and the other is that chlorobenzene is taken as a raw material (CN 97110835.8). Fluorobenzene is expensive, and national regulations have more and more strict restrictions on fluorine-containing compounds, so that the advantages of chlorobenzene are more and more obvious. Chinese patent CN97110835.8 discloses a process for preparing 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) butanone and 2- (4-methylbenzyl) -2-dimethylamino-1- (4-morpholinophenyl) butanone from chlorobenzene by acylation reaction to obtain 1- (4-chlorophenyl) -1-butanone, reaction with morpholine under pressure to produce 1- (4-morpholinophenyl) -1-butanone, bromination, amination and rearrangement reaction. However, when chlorobenzene is used as a raw material to prepare the alpha-aminoacetophenone photoinitiator, the key preparation step of the pressure reaction has many points to be improved:
first, 1- (4-chlorophenyl) -1-butanone presents a safety hazard during the reaction, and therefore its accumulation is properly controlled. There are two ways to control the accumulation of 1- (4-chlorophenyl) -1-butanone, one is continuous addition at reaction temperature and pressure for a long time; secondly, accelerating the reaction to a certain degree by using a catalyst such as cuprous chloride; the former has long reaction time, is dangerous to feed at high temperature and high pressure, has higher requirements on reaction equipment, and introduces heavy metal ions, and particularly has no advantages under the condition that the restriction of environmental regulations of various countries on the heavy metals is more and more strict;
secondly, the key intermediate 1- (4-morpholinyl phenyl) -1-butanone contains black substances of byproducts, activated carbon is needed for decoloring, the post-treatment is complicated, and the activated carbon is easy to penetrate and filter during the filtration. Therefore, the process has poor industrial operability and is not suitable for industrial production.
Disclosure of Invention
The invention aims to overcome the defects of a method for preparing 1- (4-morpholinylphenyl) -1-butanone by using chlorobenzene as a raw material in CN97110835.8, and provides a preparation method of an alpha-aminophenylacetophenone photoinitiator intermediate, which does not need to add a heavy metal catalyst, does not need to add materials at high temperature and high pressure, has simple post-treatment and good product appearance and is suitable for industrial production.
The preparation method of photoinitiator 369 and 379 intermediate 1- (4-morpholinylphenyl) -1-butanone provided by the invention is characterized by comprising the following steps:
1) dissolving morpholine in water, adding 1- (4-chlorphenyl) -1-butanone, placing in a high-pressure kettle, heating to 230 ℃ within 1-2h, controlling the pressure in the kettle to 18-21bar, and keeping the temperature for reaction after stabilization;
2) after the reaction is finished, cooling and crystallizing, and directly carrying out suction filtration and purification on the product;
wherein the ratio of the 1- (4-chlorphenyl) -1-butanone and the morpholine to the water is selected from the substances with the mass ratio of 1: (3-4): (18-32).
The preparation method of 1- (4-morpholinylphenyl) -1-butanone provided by the invention can be used for preparing a product without black byproducts, has good appearance and high purity, can be used for preparing a beige product by directly crystallizing and filtering from a reaction system, and has the yield of over 90 percent and the product purity of over 99 percent. It is not necessary to use activated carbon for decolorization.
According to the preparation method of 1- (4-morpholinylphenyl) -1-butanone provided by the invention, the mother liquor obtained after filtering the product contains excessive morpholine and morpholine hydrochloride, alkali is added for neutralization, and then the mixture of morpholine and water is recovered.
The preparation method of 1- (4-morpholinophenyl) -1-butanone provided by the invention has the advantages that the feeding ratio of 1- (4-chlorphenyl) -1-butanone and morpholine to water is very critical, the optimal reaction feeding ratio is screened out through experiments, the dosage of morpholine is 3-4 times of the dosage of 1- (4-chlorphenyl) -1-butanone, and the dosage of water is 6-8 times of the dosage of morpholine, so that the complete reaction can be ensured, and the reaction period can be shortened.
The invention is characterized in that the second characteristic is that the water consumption is increased, on one hand, the concentration of the 1- (4-chlorphenyl) -1-butanone in the reaction system can be effectively dispersed, thereby reducing the reaction risk, the materials can be fed together, on the other hand, the continuous feeding for hours under the conditions of high temperature and high pressure is avoided, the risk is reduced, and no special requirements are required for high temperature and high pressure equipment. However, if the amount of water is more than 8 times the amount of morpholine, the reaction time is prolonged, even the reaction degree is affected, and the difficulty in recovering morpholine is increased, the concentration of morpholine is low, morpholine does not azeotrope with water, different concentrations have different boiling points, and the time for recovering morpholine is too long.
The method has the third characteristic that the consumption of morpholine is reduced, the cost is saved, and the energy required by subsequent recovery of morpholine is also reduced, but the consumption of morpholine is not less than 3 times of that of 1- (4-chlorphenyl) -1-butanone, so that the reaction degree and the reaction rate are influenced, the theoretical consumption of morpholine is 2 times of that of 1- (4-chlorphenyl) -1-butanone, but the morpholine is in a gas-liquid coexisting state at high temperature and high pressure, and part of morpholine exists in a gas state, so that the concentration of morpholine in the reaction liquid is reduced.
In addition, the amount of water is increased, the amount of morpholine is reduced, the heating time of the product in recovering morpholine is reduced by separating the product from the reaction solution, and the generation of black byproducts can be reduced, so that the product can be obtained without activated carbon and recrystallization, and the reaction period is shortened.
The preparation method of 1- (4-morpholinylphenyl) -1-butanone provided by the invention can effectively prepare the photoinitiators 369 and 379, and the 1- (4-morpholinylphenyl) -1-butanone wet product obtained by spin-filtration can be directly used for subsequent reaction in the actual preparation process of the photoinitiators 369 and 379 without a drying process.
Compared with the prior art, the preparation method of the alpha-aminoacetophenone photoinitiator intermediate 1- (4-morpholinylphenyl) -1-butanone provided by the invention has many advantages:
1. morpholine, water and 1- (4-chlorphenyl) -1-butanone serving as reaction raw materials can be added into a high-pressure reaction kettle together before heating and high pressure without safety risk, and continuous feeding is carried out for hours under the condition of avoiding high temperature and high pressure;
2. the product has good appearance, does not contain gray byproducts, and avoids the decolorization by using activated carbon;
3. the reaction effect is good, the crystallization, filtration and purification can be directly carried out in the reaction liquid, the subsequent recrystallization process is not needed, and the post-treatment is simple;
4. the product is separated firstly, and then the morpholine is recovered, so that the influence on the appearance of the product caused by long-time heating during morpholine recovery can be avoided.
The specific embodiment is as follows:
in order to illustrate the invention more clearly, the following non-limiting examples are given for further illustration.
Example 1: preparation of 1- (4-morpholinophenyl) -1-butanone
Dissolving morpholine (336.5 g, 4.0 mol) in water (360.0 g, 20.0 mol), then adding 1- (4-chlorphenyl) -1-butanone (182.7, 1.0 mol), stirring uniformly, adding into a 1.5L high-pressure reaction kettle, closing the reaction kettle, heating the reaction liquid to 210-215 ℃ within 1.5-2h, simultaneously raising the pressure in the reaction kettle, controlling the pressure in the kettle to be about 20bar, carrying out heat preservation reaction for about 8h, then cooling, crystallizing, carrying out spin filtration, washing a filter cake with water, and drying to obtain 222.8g of beige crystals, wherein the purity is 99.1%, and the melting point is 65.5-66.5 ℃.
After centrifugation, the filtrate was collected for morpholine recovery, and 40.0g of sodium hydroxide was added with stirring. After the addition, the mixture fraction of morpholine and water is collected by heating and distillation for direct use.
Example 2: preparation of 1- (4-morpholinophenyl) -1-butanone
Dissolving morpholine (261.0 g, 3.0 mol) in water (360.0 g, 20.0 mol), then adding 1- (4-chlorphenyl) -1-butanone (182.7, 1.0 mol), stirring uniformly, adding into a 1.5L high-pressure reaction kettle, closing the reaction kettle, heating the reaction liquid to 210-215 ℃ within 1.5-2h, simultaneously raising the pressure in the reaction kettle, controlling the pressure in the kettle to be about 20bar, carrying out heat preservation reaction for about 10h, then cooling, crystallizing, carrying out spin filtration, washing a filter cake with water, and drying to obtain 220.8g of beige crystals, wherein the purity is 99.3%, and the melting point is 65.5-66.5 ℃.
Example 3: preparation of 1- (4-morpholinophenyl) -1-butanone
Dissolving morpholine (217.5 g, 2.5 mol) in water (360.0 g, 20.0 mol), then adding 1- (4-chlorphenyl) -1-butanone (182.7, 1.0 mol), stirring uniformly, adding the mixture into a 1.5L high-pressure reaction kettle, closing the reaction kettle, heating the reaction solution to 210-215 ℃ within 1.5-2h, simultaneously increasing the pressure in the reaction kettle, controlling the pressure in the kettle to be about 20bar, carrying out heat preservation reaction for about 28h, then cooling, crystallizing, carrying out spin filtration, washing a filter cake with water, and drying to obtain 186.0g of beige crystals with the purity of 93.5%.
Example 4: preparation of 1- (4-morpholinophenyl) -1-butanone
Morpholine (336.5 g, 4.0 mol) is dissolved in water (360.0 g, 20.0 mol), then 1- (4-chlorphenyl) -1-butanone (182.7, 1.0 mol) is added, after even stirring, the mixture is added into a 1.5L high-pressure reaction kettle, the reaction kettle is closed, the reaction liquid is heated to 210 ℃ and 215 ℃ within 1.5-2h, the pressure in the reaction kettle is increased, the pressure in the reaction kettle is controlled to be about 20bar, the reaction is kept for about 8h, then the reaction is cooled to room temperature, and 40.0g of sodium hydroxide is added under stirring. After the addition is finished, heating, distilling and collecting all morpholine and water mixture fractions, then cooling, crystallizing, filtering, washing filter cakes with water, and drying to obtain dark beige crystals 210.2 with the purity of 98.5%.
Example 5: preparation of 1- (4-Morpholphenyl) -1-butanone (using the reference without catalyst)
1- (4-chlorphenyl) -1-butanone (164.4 g, 0.9 mol), morpholine (313.2 g, 3.6 mol), and water (324.0 g, 18.0 mol) are added into a 1L high-pressure reaction kettle, the reaction kettle is closed, the temperature is raised to 180 ℃ within 1h, then the reaction liquid is further slowly heated, the temperature is raised to about 10 ℃ per hour, 4 hours are carried out, the temperature of the reaction liquid reaches 220 ℃, the pressure reaches 22bar, the reaction is continuously reacted for 5 hours at 220 ℃, the pressure is slowly reduced to 18.5bar, then the reaction liquid is cooled and crystallized, the filter cake is washed by water and dried, 219.6g of beige crystals are obtained, and the purity is 99.2%.
Example 6: preparation of 1- (4-Morpholphenyl) -1-butanone (direct filtration work-up of the reference)
392.1g (4.5 mol) of morpholine and 162.0g (9.00 mol) of water are added into a 1L high-pressure reactor, the reaction kettle is closed, the temperature is raised to 220 ℃ about 1 hour, 164.4g (0.9 mol) of 1- (4-chlorphenyl) -1-butanone is uniformly added within 5 hours at the temperature, the heat preservation reaction is carried out for 5 hours after the addition, then the temperature is reduced, crystallization is carried out, the filter cake is thrown and filtered, washed by water and dried, 209.6g of blackened crystals with the purity of 97.2 percent are obtained.
Example 7: preparation of 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) -1-butanone
Taking the dried product 1- (4-morpholinyl phenyl) -1-butanone (46.7 g, 0.20 mol) prepared in the method of example 1 to dissolve in 100ml of toluene, stirring uniformly, dripping 4.7g of concentrated sulfuric acid under ice-water bath, heating to room temperature after 0.5h dripping, dripping bromine (25.6 g, 0.16 mol) dissolved in 40ml of toluene in advance into a reaction system, keeping the temperature for reaction after 1h dripping, monitoring the reaction by TLC or liquid chromatography, adding 47ml of water after the reaction is completed, stirring for 0.5h, standing for layering, separating out a water phase, extracting with 40ml of toluene, combining toluene phases, washing with a saturated sodium carbonate solution, and obtaining an organic phase, namely a toluene solution of 2-bromo-1- (4-morpholinyl phenyl) -1-butanone with the liquid phase content of 97.8%. Directly transferring the liquid phase into a 1L four-mouth bottle, adding 45g of 40% dimethylamine aqueous solution (18 g, 0.4 mol) and sodium carbonate (21.2 g, 0.2 mol), stirring at room temperature for reaction, monitoring the reaction by TLC or liquid chromatography, standing for layering after the reaction is completed, separating out an organic phase, washing with water to obtain a toluene solution of 2-dimethylamino-1- (4-morpholinylphenyl) -1-butanone with the liquid phase content of 96.5%, transferring into a 1L four-mouth bottle, heating to 70-80 ℃, adding benzyl chloride (30.4 g, 0.24 mol), keeping the temperature for reaction, monitoring the reaction by TLC, slowly dripping 15% sodium hydroxide solution (16.0 g, 0.4 mol) into the reaction system after the reaction is completed, reacting for 2h after dripping, reducing the temperature to room temperature, standing for layering, separating out an organic phase, extracting an aqueous phase by 40ml toluene, combining toluene phases, washing by 100ml water, after the organic phase was desolventized, ethanol was added to the residue to conduct recrystallization, whereby 65.2g of 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) -1-butanone, which was pale yellow crystals, was obtained with a purity of 99.3%.
Example 8: preparation of 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) -1-butanone
49.16g (water content: 5%) of wet 1- (4-morpholinophenyl) -1-butanone prepared by the method of example 1 is dissolved in 150ml of toluene, stirred uniformly, heated under reflux to dehydrate until the water content is complete, cooled to room temperature, 4.7g of concentrated sulfuric acid is added dropwise in an ice water bath, after 0.5h of dropwise addition, the temperature is raised to room temperature, bromine (25.6 g, 0.16 mol) dissolved in 40ml of toluene in advance is added dropwise into the reaction system, 1h of dropwise addition is completed, the reaction is carried out under the condition of heat preservation, TLC or liquid chromatography monitoring is carried out, after the reaction is complete, 47ml of water is added, the mixture is stirred for 0.5h, the mixture is kept stand and layered, an aqueous phase is separated, 40ml of toluene is used for extraction, a toluene phase is combined, the toluene phase is washed by a saturated sodium carbonate solution, and the obtained organic phase, namely a toluene solution of 2-bromo-1- (4-morpholinophenyl) -1-butanone is obtained, and the liquid phase content is 97.8%. Directly transferring the liquid phase into a 1L four-mouth bottle, adding 45g of 40% dimethylamine aqueous solution (18 g, 0.4 mol) and sodium carbonate (21.2 g, 0.2 mol), stirring at room temperature for reaction, monitoring the reaction by TLC or liquid chromatography, standing for layering after the reaction is completed, separating out an organic phase, washing with water to obtain a toluene solution of 2-dimethylamino-1- (4-morpholinylphenyl) -1-butanone with the liquid phase content of 96.5%, transferring into a 1L four-mouth bottle, heating to 70-80 ℃, adding benzyl chloride (30.4 g, 0.24 mol), keeping the temperature for reaction, monitoring the reaction by TLC, slowly dripping 15% sodium hydroxide solution (16.0 g, 0.4 mol) into the reaction system after the reaction is completed, reacting for 2h after dripping, reducing the temperature to room temperature, standing for layering, separating out an organic phase, extracting an aqueous phase by 40ml toluene, combining toluene phases, washing by 100ml water, after the organic phase was desolventized, ethanol was added to the residue to conduct recrystallization, whereby 65.5g of 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) -1-butanone, which was pale yellow crystals, was obtained with a purity of 99.1%.
Claims (1)
1. A preparation method of 1- (4-morpholine phenyl) -1-butanone is characterized by comprising the following specific steps:
1) dissolving morpholine in water, adding 1- (4-chlorphenyl) -1-butanone, placing in a high-pressure kettle, heating to 230 ℃ within 1-2h, controlling the pressure in the kettle to 18-21bar, and keeping the temperature for reaction after stabilization;
2) after the reaction is finished, cooling and crystallizing, and directly carrying out suction filtration and purification on the product;
wherein the ratio of the 1- (4-chlorphenyl) -1-butanone and the morpholine to the water is selected from the substances with the mass ratio of 1: (3-4): (18-32).
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| CN112047903B (en) * | 2020-08-12 | 2022-09-13 | 浙江天成工程设计有限公司 | Device for synthesizing 2-benzyl-2-dimethylamino-1- (4-morpholinylphenyl) butanone and application of device |
| CN114315760A (en) * | 2021-12-29 | 2022-04-12 | 内蒙古久日新材料有限公司 | Preparation method and application of 2-chloro-1- (4-morpholinylphenyl) -1-butanone |
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